Cancer in children and adolescents in Spain: incidence, treatment setting and provider specialty.

PURPOSE: To analyze cancer incidence, distribution of malignancy, treatment setting and provider specialty of cancer patients, 0-19 years old, in the Comunitat Valenciana, Spain. METHODS/PATIENTS: All incident childhood and adolescent (0-19 years) cancer cases registered in the population-based Comunitat Valenciana Childhood Cancer Registry (RTICV) from 2007 to 2010 were included. Pathological and hematological diagnoses were recoded using the International Classification of Childhood Cancer Third Edition (ICCC-3). Treatment setting and provider specialty were analyzed. RESULTS: 696 patients <20 years were diagnosed with cancer: 513 cases were children (0-14 years) and 183 were adolescents (15-19 years). Overall age-adjusted incidence for 2007-2010 was 176.0 cases per million (95 % CI 162.8-189.2), with incidence being the highest among infants (287.4), followed by 1-4 years (205.5), adolescents (179.9), 10-14 years (150.2) and 5-9 years (140.6). Among adolescents aged 14-19 years, the treatment setting differed by cancer type; 87 % of them were never seen at pediatric oncology units, while 40 % were treated in up to 20 different medical oncology departments in institutions without pediatric oncology expertise. CONCLUSIONS: This is the first population-based epidemiological study carried out in Spain on children and adolescents with cancer. Centralization of care to a small number of specialized centers and thorough pediatric and oncology team collaboration are needed to improve care and survival for adolescents with cancer in our country. We suggest the creation of specific adolescent tumor boards in main tertiary care hospitals, in which adolescents with cancer can benefit from the shared expertise of medical and pediatric specialists.

[Adjuvant and salvage radiotherapy after radical prostatectomy]. / Tratamiento adyuvante y de rescate tras prostatectomía radical.

After radical prostatectomy is important to identify patients who have a high risk of microscopic residual disease without micrometastatic disease. Adjuvant RT, in retrospective studies, reduce the risk of recurrence and is more efficacious than salvage RT and can improve PSA relapse-free survival and should have an impact on long-term overall survival. The benefit of androgen suppression could be due to a synergistic interaction and may possibly eliminate occult systemic disease. Appropriate selection to identify subgroups of patients who may benefit from salvage RT, even for those patients at the highest risk; and whether some form of hormone ablation should accompany. To predict the biochemical failure and the risk of metastatic disease after salvage RT. We analyze the references to select an appropriate therapy. Improved outcomes will need to be tested in randomized trials.

Tratamiento adyuvante y de rescate tras prostatectomía radical / Adyuvant and salvage radiotherapy after radical prostatectomy

Tras la prostatectomía radical es importante identificar pacientes con alto riesgo de enfermedad microscópica residual en ausencia de enfermedad micrometastásica. La radioterapia adyuvante en estudios retrospectivos reduce las recurrencias locales y es más eficaz que la RT de rescate, aportando mejor supervivencia libre de recaída bioquímica y un potencial impacto en la supervivencia global. La supresión androgénica puede posiblemente eliminar la enfermedad oculta y aportar un efecto aditivo sobre el control local. Es posible identificar y seleccionar los pacientes que pueden beneficiarse de la Radioterapia de rescate, incluso los de alto riesgo. Se puede determinar la predicción de la progresión de PSA tras rescate con radioterapia y el riesgo de metástasis. Analizamos la bibliografía para un mejor enfoque terapéutico, basándonos en los datos actuales conocidos, a la espera de realización de nuevos ensayos clínicos (AU)

After radical prostatectomy is important to identify patients who have a high risk of microscopic residual disease without micrometastatic disease. Adyuvant RT, in retrospective studies, reduce the risk of recurrence and is more efficacious than salvage RT and can improve PSA relapse-free survival and should have an impact on long-term overall survival. The benefit of androgen suppresion could be due to a synergistic interaction and may possibly eliminate occult systemic disease. Appropiate selection to identify subgroups of patients who may benefit from salvage RT, even for those patients at the highest risk; and whether some form of hormone ablation should accompany. To predict the biochemical failure and the risk of metastasic disease after salvage RT. We analize the references to selection an appropiate therapy. Improves outcomes will need to be tested in randomized trials (AU)

Influence of ruminal distribution on norfloxacin pharmacokinetics in adult sheep.

Norfloxacin (NF) ruminal distribution after intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration was determined in order to assess the influence of the rumen on the pharmacokinetic behaviour of NF in sheep. Norfloxacin concentrations in rumen were detected after i.v. and i.m. administrations between 4 and 48 h in all animals studied. The experimental distribution ratios after i.v. and i.m. administration expressed as area under the concentration-time curve ratios AUC(rumen)/AUC(plasma) were 0.24 and 0.39, respectively, and thus lower than corresponding predicted value of 5.06. Apparently, drug persisted in the rumen content longer than in plasma. The experimental mean residence time ratios MRT(rumen)/MRT(plasma) after i.v. and i.m. administrations were 2.33 and 1.66, respectively. After p.o. administration, NF concentrations in the rumen content were extremely high compared with the respective plasma concentrations, resulting in mean peak concentrations ratio C(max-rumen)/C(max-plasma) of 383.66 and AUC(rumen)/AUC(plasma) experimental ratio of 402.32. This value was considerably higher (approximately 79 fold) than the predicted distribution ratio of 5.06. Our results suggest that the limited p.o. bioavailability of NF in ruminants could not be attributed to ruminal degradation.

Pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in adult goats.

The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose intravenous (i.v.) and intramuscular (i.m.) administrations of 2 mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography (HPLC) and the data collected were subjected to compartmental and noncompartmental kinetic analysis. This compound presented a relatively high volume of distribution (Vss=1.31 L/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.23 L/kg small middle doth, which is related to a long elimination half-life (t1/2beta=7.18 h and 6.70 h i.v. and i.m., respectively). Pharmacokinetic parameters were not significantly different between both routes of administration. Marbofloxacin was rapidly absorbed after i.m. administration (Tmax=0.9 h) and had high bioavailability (F=100.74%).

Haemorrhagic septicaemia by Aeromonas salmonicida subsp. salmonicida in a black-tip reef shark (Carcharhinus melanopterus).

One black-tip reef shark (Carcharhinus melanopterus) was found dead without previous signs of disease. Major lesions consisted in cutaneous erythema, mainly at the base of the fins, focal to diffuse inflammatory lesions in gills and intestinal wall, and discrete haemorrhages in the same organs, liver and kidneys. Microcolonies of Gram-negative rods were observed in the lamina propia of gills, underneath the intestinal mucosa and randomly distributed in the renal and hepatic parenchymas. Also, emboli containing Gram-negative rods were observed in capillaries of these organs. Aeromonas salmonicida subsp. salmonicida was isolated in pure culture from gills, liver and intestine. Specific immunostaining confirmed the relationship between the isolate and lesion-associated bacteria. No previous reports on this infection in sharks have been found in the literature.

Effects of verapamil, sodium nitroprusside and calcium deprivation on the phenylephrine-induced contraction of smooth muscle strips from the reticular groove of adult cattle.

The effects of verapamil, sodium nitroprusside and calcium deprivation on the smooth muscle strips from the floor of the reticular groove of adult cattle were studied. The mechanical activity of the muscle strip was recorded isometrically. Contraction was induced with phenylephrine (10(-6) mol/l) in Tyrode solution. Verapamil (10(-6) mol/l) produced a high inhibition of the response, phasic and tonic (P < 0.05). Sodium nitroprusside (10(-6) mol/l) reduced mainly the phasic contraction (P < 0.05). Deprivation of Ca2+ from extracellular medium produced a high inhibition of the tonic phase. This study indicates that the action of verapamil on the reticular groove smooth muscle may be partially related to blockade of calcium entry through voltage-dependent channels, opened during phenylephrine stimulation. However, the nitroprusside action could be attributed to effect on the extrusion of calcium.

Age-related differences in norfloxacin pharmacokinetic behaviour following intravenous and oral administration in sheep.

The pharmacokinetics of norfloxacin after intravenous (i.v.) and oral (PO) administration in lambs (n = 5) and adult sheep (n = 5) were studied. After i.v. administration (10 mg.kg-1) plasma concentrations were best fitted by a three-compartment open model in both age groups. Distribution volumes were significantly larger in lambs (approximate 4.0 fold difference between 4 week old and adult sheep). There was no significant difference (p < 0.05) between the groups in terms of elimination halflife but plasma clearance was significantly higher in lambs. Norfloxacin was poorly absorbed after oral administration (60 mg.kg-1) in sheep (F = 4.04%). Mean oral bioavailability was 73.51% in lambs (30 mg.kg-1). Norfloxacin elimination was faster in lambs after oral administration. MRTt was significantly prolonged in both age groups when compared with the respective data for i.v. administration.

Comparison of the kinetics of sodium meclofenamate versus meclofenamic acid after oral administration to sheep.

Meclofenamates are non-steroidal anti-inflammatory agents used in ruminants for the prevention and the treatment of anaphylactic processes. The objective of the present work was to study possible kinetic variations due to the chemical form of meclofenamates administered by the oral route to adult sheep. Six Rubia del Molar female sheep (2-3 years old, 47-57 kg) were used. Initially, an intravenous administration of sodium meclofenamate (2.2 mg/kg bwt) was given; the obtained kinetic results were in agreement with data from other authors. Oral administrations (20 mg/kg bwt) of sodium meclofenamate and meclofenamic acid were then given. When the reticular groove was opened, both drug forms showed a single meclofenamate plasma peak; t2max were 60.0 +/- 10.61 min and 127.50 +/- 22.5 min for the sodium and acid form, respectively. The elimination rate constants (beta) were not significantly different, but the absorption half-lives were (14.69 +/- 3.21 min for the sodium form and 61.07 +/- 21.7 min for the acid form). The bioavailability was 48.6 +/- 4.3% for sodium meclofenamate and 65.1 +/- 2.8% for meclofenamic acid. Thus, the chemical form (sodium versus acid) alters the oral bioavailability and tmax of meclofenamates in adult sheep. These findings agree with the behaviour of meclofenamates in man.

Effects of verapamil, sodium nitroprusside, tetrodotoxin and caffeine on the electrical transmural stimulation induced contraction in the reticular groove smooth muscle of adult cattle.

The effect of electrical transmural stimulation (ETS) on smooth muscle strips in the floor of reticular groove of adult cattle was studied. The mechanical activity of the muscle strips was recorded isometrically. ETS (4 ms, 5 s, supramaximal voltage) caused frequency dependent (2-30 Hz) contractions of this smooth muscle. An increase in cytoplasmatic free calcium concentration can be achieved by release of the cation from intracellular store sites or by an influx of extracellular Ca2+ through calcium channels. The contractile response of the muscle strips was inhibited about 66% when it was incubated in a calcium-free EGTA-containing solution. The excitatory effect of ETS was not antagonized by verapamil (10(-6) mol/l), sodium nitroprusside (10(-6) mol/l) or tetrodotoxin (10(-6) mol/l). The electrically-evoked contraction was inhibited strongly (92%) by caffeine (30 mmol/l). The contractions of the smooth muscle from the reticular groove smooth muscle are dependent on the concentration of free calcium in the cell cytosol. This response was intracellular Ca2+ ion dependent.